As the continuous development of the industrial revolution, nanomaterials with excellent characteristics have been widely applied in various fields, greatly increasing the probability of human exposure to nanomaterials and the concerns about the potential nanotoxicity. Existing studies have shown that the toxicity of nanomaterials may be closely related to oxidative stress, inflammatory response, phagocytosis dysfunction, DNA damage, etc. Based on our focus, nanomaterials may cross the human barrier through various channels and disrupt various cell-cell junctions, while the integrity of cellular barrier is a necessary for the normal physiological function of various organs. However, until now, there is still a lack of systematic discussion in this field. This review illustrates the importance of cell-cell junctions in maintaining various organ functions and highlights the mechanism of various nanomaterials disrupt cell-cell junctions, as well as the possible damage to various organs, such as brain, eye, lung, breast, intestine, placenta, testis, heart, liver, kidney, skin, etc. Awareness of the potential negative effects of nanomaterials will help scientists deeply understand the limitations of nanotechnology, inspiring them to develop safer and more efficient nanomaterials for future personalized nanomedicine.